The role of invariant natural killer T cells in experimental xenobiotic-induced cholestatic hepatotoxicity

Cheng, Nong; Zou, Mengzhi; Xue, Rufeng; Bai, Li; Liu, Li; Jiang, Zhenzhou; Sun, Lixin; Huang, Xin; Zhang, Luyong; Wang, Xinzhi

doi:10.1016/j.biopha.2019.109579

Cited by 10 publications

(12 citation statements)

References 49 publications

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“…In regard to DILI, there are conflicting results. While some studies show an increase in iNKT after triptolide [ 42 ] and alpha-naphthylisothiocyanate treatment [ 20 ], others observe a decrease in acetaminophen-treated mice [ 43 ]. However, these studies were carried out in the liver of animal models, and data on peripheral iNKT cells were not reported.…”

Section: Discussionmentioning

confidence: 99%

“…In this context, natural killer T (NKT) cells are the main innate-like T cells in the liver of both mice and humans [ 18 ]. Invariant NKT (iNKT) cells are a cell sub-population known to cause inflammation in liver [ 19 , 20 ]. Nonetheless, the activation profile and the mechanism by which iNKT cells are involved in NAFLD progression and DILI in humans remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Differential iNKT and T Cells Activation in Non-Alcoholic Fatty Liver Disease and Drug-Induced Liver Injury

et al. 2021

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Background: Non-alcoholic fatty liver disease (NAFLD) and idiosyncratic drug-induced liver injury (DILI) could share molecular mechanisms involving the immune system. We aimed to identify activation immunological biomarkers in invariant natural killer T (iNKT) and CD4/CD8+ T cells in NAFLD and DILI. Methods: We analyzed the activation profile (CD69, CD25, and HLA-DR) and natural killer group 2 member D (NKG2D) on iNKT cells, and CD4/CD8 T cells in peripheral blood mononuclear cells from NAFLD, with or without significant liver fibrosis, and DILI patients. Results: There was an increase in iNKT cells in NAFLD patients compared to DILI or control subjects. Regarding the cellular activation profile, NAFLD with significant liver fibrosis (F ≥ 2) displayed higher levels of CD69+iNKT cells compared to NAFLD with none or mild liver fibrosis (F ≤ 1) and control patients. CD69+iNKT positively correlated with insulin resistance, aspartate aminotransferase (AST) level, liver fibrosis-4 index (FIB4) and AST to Platelet Ratio Index (APRI). DILI patients showed an increase in CD69+ and HLA-DR+ in both CD4+ and CD8+ T cells, detecting the most relevant difference in the case of CD69+CD8+ T cells. Conclusions: CD69+iNKT may be a biomarker to assess liver fibrosis progression in NAFLD. CD69+CD8+ T cells were identified as a potential distinctive biomarker for distinguishing DILI from NAFLD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential iNKT and T Cells Activation in Non-Alcoholic Fatty Liver Disease and Drug-Induced Liver Injury

et al. 2021

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“…Frontiers in Pharmacology frontiersin.org resulting in downregulated expression levels of liver nuclear receptor FXR, bile acid transporter organic aniontransporting polypeptide 2b1 (OATP2B1), and CYP450 enzymes, ultimately exacerbating TP-induced cholestatic liver injury (Zou et al, 2020).…”

Section: Figurementioning

confidence: 99%

“…Natural Killer T (NKT) cells express both NK and T cell surface markers, linking innate and adaptive immunity ( Kaer et al, 2011 ). Among them, invariant NKT (iNKT) cells are a subset of cells that cause liver inflammation and play a pathogenic role ( Maricic et al, 2018 ; Marrero et al, 2018 ; Nong et al, 2020 ). NKT, especially iNKT, cells are increasingly activated in the liver after TP administration, resulting from the upregulation of the Toll-like receptor (TLR) signaling pathway, which mainly releases the Th1 cytokine interferon gamma (IFN-γ), recruits neutrophils and macrophages, and causes hepatotoxicity ( Wang X.z.…”

Section: The Mechanisms Of Tp-induced Hepatotoxicitymentioning

confidence: 99%

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The molecular pathogenesis of triptolide-induced hepatotoxicity

Wang

et al. 2022

Front. Pharmacol.

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Triptolide (TP) is the major pharmacologically active ingredient and toxic component of Tripterygium wilfordii Hook. f. However, its clinical potential is limited by a narrow therapeutic window and multiple organ toxicity, especially hepatotoxicity. Furthermore, TP-induced hepatotoxicity shows significant inter-individual variability. Over the past few decades, research has been devoted to the study of TP-induced hepatotoxicity and its mechanism. In this review, we summarized the mechanism of TP-induced hepatotoxicity. Studies have demonstrated that TP-induced hepatotoxicity is associated with CYP450s, P-glycoprotein (P-gp), oxidative stress, excessive autophagy, apoptosis, metabolic disorders, immunity, and the gut microbiota. These new findings provide a comprehensive understanding of TP-induced hepatotoxicity and detoxification.

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CXCL10 and its receptor in patients with chronic hepatitis B and their ability to predict HBeAg seroconversion during antiviral treatment with TDF

Yang,

Xu,

Cheng

et al. 2024

Journal of Medical Virology

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The serum chemokine C‐X‐C motif ligand‐10 (CXCL10) and its unique receptor (CXCR3) may predict the prognosis of patients with chronic hepatitis B (CHB) treated with tenofovir disoproxil fumarate (TDF). Nevertheless, there are few reports on the profile of CXCL10 and CXCR3 and their clinical application in HBeAg (+) CHB patients during TDF antiviral therapy. CXCL10 and CXCR3 were determined in 118 CHB patients naively treated with TDF for at least 96 weeks at baseline and at treatment weeks 12 and 24. In addition, gene set enrichment analysis was used to examine the associated dataset from Gene Expression Omnibus and explore the gene sets associated with HBeAg seroconversion (SC). The change of CXCL10 (ΔCXCL10, baseline to 48‐week TDF treatment) and CXCR3 (ΔCXCR3) is closely related to the possibility of HBeAg SC of CHB patients under TDF treatment. Immunohistochemical analysis of CXCL10/CXCR3 protein in liver tissue shows that there is a significant difference between paired liver biopsy samples taken before and after 96 weeks of successful TDF treatment of CHB patients (11 pairs) but no significance for unsuccessful TDF treatment (14 pairs). Multivariate Cox analysis suggests that the ΔCXCL10 is an independent predictive indicator of HBeAg SC, and the area under the receiver operating characteristic curve of the ΔCXCL10 in CHB patients is 0.8867 (p < 0.0001). Our results suggest that a lower descending CXCL10 level is associated with an increased probability of HBeAg SC of CHB patients during TDF therapy. Moreover, liver tissue CXCL10 might be involved in the immunological process of HBeAg SC.

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The role of invariant natural killer T cells in experimental xenobiotic-induced cholestatic hepatotoxicity

Cited by 10 publications

References 49 publications

Differential iNKT and T Cells Activation in Non-Alcoholic Fatty Liver Disease and Drug-Induced Liver Injury

Differential iNKT and T Cells Activation in Non-Alcoholic Fatty Liver Disease and Drug-Induced Liver Injury

The molecular pathogenesis of triptolide-induced hepatotoxicity

CXCL10 and its receptor in patients with chronic hepatitis B and their ability to predict HBeAg seroconversion during antiviral treatment with TDF

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